The potent anti-inflammatory effect of Guilu Erxian Glue extracts remedy joint pain and ameliorate the progression of osteoarthritis in mice

Abstract

BackgroundOsteoarthritis (OA) is a slow progressing, degenerative disorder of the synovial joints. Guilu Erxian Glue (GEG) is a multi-component Chinese herbal remedy with long-lasting favorable effects on several conditions, including articular pain and muscle strength in elderly men with knee osteoarthritis. The present study aimed to identify the effects of Guilu Erxian Paste (GE-P) and Liquid (GE-L) extracted from Guilu Erxian Glue in anterior cruciate ligament transection (ACLT)-induced osteoarthritis mice, and to compare the effectiveness of different preparations on knee cartilage degeneration during the progression of osteoarthritis.MethodsMale C57BL/6J mice underwent anterior cruciate ligament transection to induce mechanically destabilized osteoarthritis in the right knee. 4 weeks later, the mice were orally treated with PBS, celecoxib (10 mg/kg/day), Guilu Erxian Paste (100 or 300 mg/kg/day), and Guilu Erxian Liquid (100 or 300 mg/kg/day) for 28 consecutive days. Von Frey and open-field tests (OFT) were used to evaluate pain behaviors (mechanical hypersensitivity and locomotor performance). Narrowing of the joint space and osteophyte formation were examined radiographically. Inflammatory cytokine (IL-1β, IL-6, and TNF-α) levels in the articular cartilage were determined by quantitative real-time PCR. Histopathological examinations were conducted to evaluate the severity and extent of the cartilage lesions.ResultsGuilu Erxian Paste and Guilu Erxian Liquid (300 mg/kg/day) were significantly more effective (p < 0.01) than celecoxib (10 mg/kg/day) in decreasing secondary allodynia when compared to the saline-treated group (#p < 0.05). Open-field tests revealed no significant motor dysfunction between the Guilu Erxian Paste- and Guilu Erxian Liquid-treated mice compared to the saline-treated mice. Radiographic findings also confirmed that the administration of Guilu Erxian Paste and Guilu Erxian Liquid (100 and 300 mg/kg/day) significantly and dose-dependently reduced osteolytic lesions and bone spur formation in the anterior cruciate ligament transection-induced osteoarthritis mice when compared to the saline-treated group. Notably, Guilu Erxian Liquid (100 mg/kg/day) treatment significantly reduced the mRNA levels of IL-1β, IL-6, and TNF-α as well as relative the protein expression of IL-1β and TNF-α to the effect of celecoxib. Guilu Erxian Paste and Guilu Erxian Liquid (300 mg/kg/day) markedly attenuated cartilage destruction, surface unevenness, proteoglycan loss, chondrocyte degeneration, and cartilage erosion in the superficial layers (##p < 0.01 and ###p < 0.001 respectively).ConclusionsAs expected, our findings suggest that the anti-inflammatory effects of Guilu Erxian Liquid (GE-L), following marked decrease on both IL-1β and TNF-α during the early course of post-traumatic osteoarthrosis (OA), may be of potential value in the treatment of osteoarthritis.